CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance.
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Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF
CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance.
Drug Metab Dispos. 2010 Sep;38(9):1393-6. doi: 10.1124/dmd.110.033878. Epub 2010 Jun 22.
- PubMed ID
- 20570945 [ View in PubMed]
- Abstract
Clonidine is a centrally acting, alpha-2 adrenergic agonist used for the treatment of hypertension during pregnancy. The metabolic pathways of clonidine are poorly understood, and the quantitative contribution of specific human cytochrome P450 (P450) isoforms has not been systematically assessed. In this study, 17 cDNA-expressed P450 enzymes, in addition to pooled human liver microsomes, were evaluated for clonidine 4-hydroxylation activity in vitro. Five P450 enzymes-CYP2D6, 1A2, 3A4, 1A1, and 3A5-catalyzed measurable formation of 4-hydroxyclonidine. Selective inhibition studies in human liver microsomes confirmed that these isoforms are jointly responsible for 4-hydroxylation of clonidine in vitro, and CYP2D6 accounted for approximately two-thirds of the activity. The major role of CYP2D6 in clonidine metabolism might explain the increase in its nonrenal clearance during pregnancy.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Clonidine Cytochrome P450 1A1 Protein Humans UnknownSubstrateDetails Clonidine Cytochrome P450 1A2 Protein Humans UnknownSubstrateDetails Clonidine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Clonidine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Clonidine Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails - Drug Reactions
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